Breast fed children tend to be healthier, with lower incidence of allergy and infectious disease, and tend to be leaner than formula fed children [1]. Although the reasons for these protective effects are not completely understood, milk proteins clearly play a role. In addition, previous studies have demonstrated that human milk proteins influence gastrointestinal, neural, and immunologic development in the nursing infant [2-6].
Adiponectin (also called ACRP30, adipoQ or GBP28), a protein produced primarily in adipose tissue by adipocytes [7-10], influences several physiologic processes that may impact human development. High concentrations of circulating adiponectin have positive health effects through the reduction of pro-inflammatory cytokines [11, 12], improvement of insulin sensitivity [13], and increase of fatty acid metabolism [14].
Human milk composition exhibits variation within and between lactating women. Intra-individual variation is likely due in part to changes in milk protein concentrations throughout lactation [15-17]. Inter-individual variability in milk protein concentrations has been attributed to genetic variation [18, 19] and maternal adiposity [20] among other factors.
In humans, adiponectin levels are inversely correlated with insulin resistance independent of adiposity [21-23], with the lowest levels of adiponectin in individuals with type 2 diabetes [24-26]. Furthermore, low adiponectin precedes the development of insulin resistance, suggesting a direct effect of adiponectin on insulin sensitivity [27-33]., Mouse studies have confirmed that adiponectin improves glucose utilization [34]. High adiponectin has also been associated with an anti-atherogenic lipid profile. Adiponectin is consistently inversely correlated with plasma triglycerides (TG) and positively correlated with plasma HDL cholesterol levels [35]. Adiponectin directly influences lipid metabolism and oxidation. Additionally, adiponectin has strong anti-inflammatory properties. Adiponectin decreases TNF-α [11] and IL-6 [11, 12] production, and increases expression of anti-inflammatory cytokines in macrophages [36]. Adiponectin also works downstream of TNF-α to suppress its ability to activate the NF-κB pathway [37]. Adiponectin inhibits the formation of granulocyte-macrophage colonies in vitro, and inhibits the phagocytic activity of mature macrophages [38].
Adiponectin exists in several oligomeric forms in vivo, the most common of which are trimers, hexamers or low molecular weight (LMW) forms, and double hexamers and higher-order structures that together are considered high molecular weight (HMW) forms.
Specific oligomers of adiponectin are associated with important metabolic outcomes in humans. The HMW form of circulating adiponectin is selectively increased in response to weight loss [39, 40] and is selectively decreased in response to infusion of insulin [41]. This is of particular interest because the HMW form of adiponectin is associated with changes in physiologic processes known to be strongly influenced by obesity: The proportion of adiponectin bound together as HMW complexes is better associated with glucose tolerance than total adiponectin levels [42]. Improvements in hepatic insulin sensitivity after treatment with anti-diabetic drugs are also more associated with the proportion of adiponectin present as HMW complexes than total adiponectin concentration [43]. HMW complexes constitute a lower percentage of total adiponectin in adults with coronary artery disease, compared with normal controls, and only the HMW form protects vascular endothelial cells from apoptosis [39]. The HMW complex is also more positively correlated with the anti-atherogenic high-density lipoprotein (HDL) cholesterol than total adiponectin, while the trimeric form is inversely associated with HDL [40].
Adiponectin oligomeric structures appear to be assembled within the cell and secreted, with little spontaneous interchange between the complexes at physiologic conditions [41, 44]. Indeed, Wang et al. [45] suggested that hydroxylation and glycosylation of specific amino acids the adiponectin gene account for the different oligomeric forms.